Dataset Information

Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene?edited cardiomyocytes.

ABSTRACT: RhoE/Rnd3 is an atypical member of the Rho superfamily of proteins, However, the global biological function profile of this protein remains unsolved. In the present study, a RhoE?knockout H9C2 cardiomyocyte cell line was established using CRISPR/Cas9 technology, following which differentially expressed genes (DEGs) between the knockout and wild?type cell lines were screened using whole genome expression gene chips. A total of 829 DEGs, including 417 upregulated and 412 downregulated, were identified using the threshold of fold changes ?1.2 and P<0.05. Using the ingenuity pathways analysis system with a threshold of ?Log (P?value)>2, 67 canonical pathways were found to be enriched. Many of the detected signaling pathways, including that of oncostatin M signaling, were found to be associated with the inflammatory response. Subsequent disease and function analysis indicated that apart from cardiovascular disease and development function, RhoE may also be involved in other diseases and function, including organismal survival, cancer, organismal injury and abnormalities, cell?to?cell signaling and interaction, and molecular transport. In addition, 885 upstream regulators were enriched, including 59 molecules that were predicated to be strongly activated (Z?score >2) and 60 molecules that were predicated to be significantly inhibited (Z?scores

SUBMITTER: Shao Z

PROVIDER: S-EPMC7388835 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes.

Shao Zhongming Z Wang Keke K Zhang Shuya S Yuan Jianling J Liao Xiaoming X Wu Caixia C Zou Yuan Y Ha Yanping Y Shen Zhihua Z Guo Junli J Jie Wei W

International journal of molecular medicine 20200626 3

RhoE/Rnd3 is an atypical member of the Rho superfamily of proteins, However, the global biological function profile of this protein remains unsolved. In the present study, a RhoE‑knockout H9C2 cardiomyocyte cell line was established using CRISPR/Cas9 technology, following which differentially expressed genes (DEGs) between the knockout and wild‑type cell lines were screened using whole genome expression gene chips. A total of 829 DEGs, including 417 upregulated and 412 downregulated, were identi ...[more]

PMID: 32705255

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Project description:Background and Aims: Familial hypercholesterolemia (FH) is one of the major risk factor for the progression of atherosclerosis and coronary artery disease. This study focused on identifying the dysregulated molecular pathways and core genes that are differentially regulated in FH and to identify the possible genetic factors and potential underlying mechanisms that increase the risk to atherosclerosis in patients with FH. Methods: The Affymetrix microarray dataset (GSE13985) from the GEO database and the GEO2R statistical tool were used to identify the differentially expressed genes (DEGs) from the white blood cells (WBCs) of five heterozygous FH patients and five healthy controls. The interaction between the DEGs was identified by applying the STRING tool and visualized using Cytoscape software. MCODE was used to determine the gene cluster in the interactive networks. The identified DEGs were subjected to the DAVID v6.8 webserver and ClueGo/CluePedia for functional annotation, such as gene ontology (GO) and enriched molecular pathway analysis of DEGs. Results: We investigated the top 250 significant DEGs (p-value < 0.05; fold two change ≥ 1 or ≤ -1). The GO analysis of DEGs with significant differences revealed that they are involved in critical biological processes and molecular pathways, such as myeloid cell differentiation, peptidyl-lysine modification, signaling pathway of MyD88-dependent Toll-like receptor, and cell-cell adhesion. The analysis of enriched KEGG pathways revealed the association of the DEGs in ubiquitin-mediated proteolysis and cardiac muscle contraction. The genes involved in the molecular pathways were shown to be differentially regulated by either activating or inhibiting the genes that are essential for the canonical signaling pathways. Our study identified seven core genes (UQCR11, UBE2N, ADD1, TLN1, IRAK3, LY96, and MAP3K1) that are strongly linked to FH and lead to a higher risk of atherosclerosis. Conclusion: We identified seven core genes that represent potential molecular biomarkers for the diagnosis of atherosclerosis and might serve as a platform for developing therapeutics against both FH and atherosclerosis. However, functional studies are further needed to validate their role in the pathogenesis of FH and atherosclerosis.

Dataset Information

Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene?edited cardiomyocytes.

Publications

Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes.

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